DIP Episode 398 - Some Pharmacology Scenarios For Step 2/3

Okay, welcome. My name is Divine. This is episode 398 of the Divine Intervention podcasts. And in today's podcast, I'm going to be addressing what I call key from archaeological mechanisms for the USML step 2 CK and step 3 exams. Although this is something that will be profoundly useful to a person that is also taking the USML step 1 exam. But really, in today's podcast, because the MBME is every now and then you see the right question. And it's basically if you hear people say, oh, you know, I see basic science on my exam, many times it's in this context where you see a question, it's a clinical pathology, but they ask for the basic science pathophysiology that underlies it. So that's what I'm going to try to address today. And as a reminder, if you're taking your step 2 or step 3 exams, actually, anytime within the next maybe like 2 or so weeks, I would encourage you to take the review course I have. It's actually starting this evening. It's starting at 5 p.m. Pacific Standard Time. We'll go for four hours each day of this week, except Wednesday, including Saturday. So, we'll Monday, Tuesday, Thursday, Friday, Saturday, and four hours each day, starting at 5 p.m. Pacific Standard Time. Again, many people have taken this course. They found it to be super, super helpful. I have people that I get very good news every Wednesday. Oh, wow, divine. I took your course. I crushed my exam. So if you're interested, just shoot me an email and I can give you some more information.

So, what if they give you a question about a patient, they tell you that this patient was brought to the emergency room by his friends because he had been completely off chest pain. And then they tell you that on EKG, they notice that his proponents, I mean, they get some labs, they notice his proponents are elevated, and they tell you that an EKG shows territorial ST segment elevations. What should you be thinking about here? And then they can ask, oh, and maybe they can even say, you know, the person is the intercalth lab and they perform coronary and geography. And it shows like 30% stenosis of his LED, right? And let's say, you know, the ST elevations we saw, we're in like V1 through V4. You're like, hmm, this is kind of weird. We have 30% stenosis and, you know, person has ST elevations in V1 to V4, right? And we know the NBM Es, they, they write their questions in a certain way, right? This is one of those things that you see me emphasizing my test taking strategies class. But for example, they'll say, oh, so what's the most likely on the line mechanism behind this patient's presentation, right? And then they can say, you know, atherosclerotic disease of the left anterior descending artery, and I'll be and they know that many people want to pick that answer. And you know why? Because they see, you know, that's probably one of the more primary reasons why you'll see, oh, coronary and geogrophysioles 30% stenosis.

Because they know, at least if they put that stenosis, they see that word. Some people in the emotional state of the exam, they go with that. But again, if you're thinking straight, you should remember that 30% stenosis is not going to cause you to have an MI. There's something else going on here. This person has visospastic disease of the coronary arteries that's causing their problems, right? I mean, this person is coming from a party, right? They're probably taking cocaine of some sort on meth, right? But basically, whenever you take any of these, sympathetic medications, they can cause coronary visospasm. The classic ones on exams, again, they're going to be cocaine, they're going to be methamphetamine. Those things, they cause you to have more caracolamines in your synapse, in your adrenergic synapses. So if you have more caracolamines, you can have a more viso-constrictive effect on your coronary vessels. And the person can get problems. They can get them on your caracolamine function that way. So that's the mechanism, right? So the mechanism is, again, from increased caracolamina availability at adrenergic synapses. Or you can see visospasim of the coronary arteries. That's what's causing the person's problems. So don't forget we're cocaine on meth. And a common question I get from students is, define how do I differentiate between cocaine intoxication and methamphetamine intoxication.

On endemic exams, methamphetamine intoxication usually presents with very prominent hallucinations. Prominent hallucinations are a very core feature of methamphetamine intoxication. That's something I want to keep at the back of your mind, for example. Cocaine intoxication classically, I'm not saying you can never, but classical unexams does not present with prominent hallucinations. But remember, it's not only cocaine on meth that can cause a visual constriction that can cause coronary visospasim. You know, people that have prince methamphetamine and gina, remember these days we give it a new name, we call it variant angina these days. But variant angina can absolutely present with coronary visospasim. And that coronary visospasim can cause problems. Classically, it's going to be in a female and she's usually going to be a smoker of some sort. And she'll have chest pain that is worse at night. And then you, again, you take out for coronary angiography, you notice that everything looks relatively clean, right? When you see that again, I want you to think of variant angina, those people respond very beautifully to calcium channel blockers. So something like an e can be a calcium channel blocker of either class, either the dihydroperidine calcium channel blockers or the non-dihydroperidine calcium channel blockers like verapameloadeltisim.

Now coronary visospasim can also be the mechanism, you know, person that they tell you that, oh, you know, a person is being treated for migraines, and then, you know, they tell you that, you know, they've been taking this medication for acute migraines. And then they present with chest pain, or you want to think about sumatriptan, right? Or those ergot agents like ergotamine, for example, those drugs can cause coronary visospasim. Because the thing is, I believe I've maybe explained this in one of my previous podcasts. But one of the primary mechanisms behind headache is visodilation. When there is visodilation in the brain, a person gets headache, okay? So if you wanted to fix that problem, you want to cause a net viso-construction in the brain. How do you do that? Well, think about it. One of the most common medications that are seeking for headaches is the, is an onset. Ence� work by inhibiting cycloxiginase. When you inhibit cycloxiginase, you decrease prostaglandin synthesis. Prostaglandin, as we know, is a permanent viso-dialiter. So, I mean, that's why we give our prostate deal. It's a PG1 analog to keep the doctors at your ears open. So you give an onset, you inhibit cycloxiginase, you make less prostaglandins, and you have a net viso-construction. And that's helpful from a headache perspective. So if you really think about it, a person that has migraines, you want to give them, at least for acute management, right?

Acute management of migraines, you want to give them drugs that can cause a net viso-construction in the brain. So much reptan is a net viso-constructor in the brain. There are ergot agents like ergotamine is a net viso-constructor in the brain. So those things, because they cause viso-construction, they're good for migraines. But again, if you really think about it, when people have touchy-filly coronary arteries, they can begin to get problems, right? Especially people that have like very antenna for example, or let's say people that have like renotes phenomenon. Those people, you want to think twice about giving them drugs like sumatriptan or they're gotamine agents, because those people, they have vessels, they have vasculature, already visospastic at baseline. So you just want to think twice about giving people those drugs, right? So for example, if a person has a history of even M.I., like they've had that M.I. before, or they've had like, you know, like just really bad vascula disease, giving those people sumatriptan may not be the smartest idea in the world, right? Because again, those things can cause coronary visospasins, right? They can absolutely cause coronary visospasins. So that's something we want to keep in mind. In fact, let me maybe go through some drugs that are contraindicated in people that have a history of prince beta-langena, right? It's going to be things like beta-blockers, beta-blockers, bad ideas, especially the non-selective beta-blockers.

Because remember, beta-to-receptors, when you activate them, they have viso-dialating receptors. But if you give a like, prepare a law, for example, that's going to block those beta-to-receptors, that's going to cause a net-visual construction, and that can be a problem for those people. So that's something we want to keep at the back of your mind, for example. And again, subatriptan, these ergod agents, not a good idea in these folks, right? Or people that have re-nodes phenomenon. Because again, remember, the pathophys behind re-nodes phenomenon is visospasim, right? They have visospasim of their digital vessels. That's why, you know, when they go out in the cold, you know, that cold kind of accelerates that visospasim and then they get in trouble. For those people, again, you want to think twice about giving them these kinds of medications. So again, I know I spent a lot of time on visospasim, but it's like a pretty high-yield concept to know for, for example. I won't be going over it in this detail. If it was something that was a fly-by-night idea for a test, it's not a fly-by-night idea. It's an idea you actually want to cement in your mind as you take your exam. Okay, now, what if they give you a question about a patient, you know, the teller that this patient presented two days ago to the emergency room with a two-week history of fevers and some malchest pain having this fluttering feeling in his chest.

And then they tell you that, you know, the person also had like a mild fever and the person had, you know, some infiltrates that we visualized in the lungs. And then they tell you that blood cultures are positive and empiric, I mean, the tell you that blood cultures have been sent, what results have not been obtained, right? And then they tell you that empiric antibiotic therapy was started. You know, and they also tell you some story about like some murmur that's been heard at the left-low external border that increases with inspiration. Well, and then they tell you that, you know, this person started on an infusion of some medication. And then the patient's skin becomes like red and things like that. But then the person's vital is all the white stable. When you see stuff like that, I really hope you're thinking about red man syndrome, right? Red man syndrome. So how do all these things kind of come together? Well, if you think about it, this person has so-and-so-beauty symptoms. It's been going on for two weeks. Persians have not been feeling well, you know, fever, you know, chest pain, infiltrates in the lungs. Those are probably septic pulmonary embolite. He may be like, wow, divine. So are you telling me that this person has endocraditis? Yes, absolutely. This person has endocraditis, right? What are some of the clues? Well, again, you see the subacute nature of the symptoms, you see the fever, you see the infiltrating the lungs, right?

Again, remember, people with endocraditis, they can have septic pulmonary embolite. And then you also notice that this person has a tricospid murmur. If you think about it, the fact that I said that you hear a murmur at the left-low external border that increases with inspiration, that's me telling you that, this is a right-sided heart murmur. This is a tricospid murmur because remember, tricospid valve anatomically is around the left-low external border. So you see that, you know, you hear this murmur, it increases with inspiration, that tells you likely a right-sided heart murmur. And why do they increase with inspiration? Again, mechanism. You think about it, when you inspire, your diaphragm goes down. When your diaphragm goes down, your intracuracy volume goes up. If your intracuracy volume goes up, your intracuracy pressure goes down, and boils low, right? Volume and pressure inversely related, boils low, probably learned it in general chemistry and college. So if the intracuracy pressure goes down, then you're creating a low pressure system in the thoracic cavity that welcomes blood back to the heart. So if you're welcoming more blood back to the right side of the heart, you're going to have more flow across the tricospid valve. If the tricospid valve is already in a ten-watt situation, then you're going to hear a murmur. Because when you have more flow across a disturbed valve, that's what's categorized as a murmur. So the person will have a tricospid murmur.

Because remember, this person probably is an IV drug user. Because if you think about it, if you're an IV drug user, well, we're getting dragged in those drugs into. I mean, literally, it's in the name, IV intravenous. You inject the drug into a vein, well, really veins draining the body, veins draining to the right side of the heart. So the first point of call for any bug that comes in is going to be the tricospid valve. So tricospid valve endocraditis is very common in IV drug users. So this person got in pyrrhic therapy because this person got a blood culture, blood cultures sometimes take a while to result. Because that's the first thing you're supposed to do for endocraditis. You're supposed to do blood cultures before you do any kind of antibiotic therapy. But we know that one of the most common causes of endocraditis is staphoreus. So the person probably got in pyrrhic therapy with vancomycin. Vancomycin. And by the way, when a person has endocraditis, they get IV antibiotics. The NBA needs the existing to do these days with it will give you an IV antibiotic answer. And then they will give you an oral antibiotic answer. You need to be careful. For certain diseases, oral antibiotics are absolutely not appropriate. Like osteomyelitis, for example, oral antibiotics, but I get for endocraditis, for example, oral antibiotics, but I get you need to use IV antibiotics in these people. So the person very likely got in pyrrhic therapy with IV vancomycin.

Well, the thing that vancomycin can do is that it can cause a person to release histamine. And that histamine release can cause visodilation. That visodilation can cause cutaneous flushing. It can cause cutaneous flushing. That's something you want to keep at the back of your mind, for example. That's red man syndrome. That's an antibiotic associated infusion reaction. Red man syndrome. Red man syndrome is caused by histamine release. And how can we reduce the risk of this happening? Where you can reduce the risk of this happening by pre-trading with an anti-histamine of some sort? Alternatively, you can also give a slower infusion. If you give the vancomycin at a high infusion rate, you're raising the person's risk of having a red man syndrome. And again, there are other things that can cause a person to have like flushing and visodilation. Remember the drug adenosine. Remember adenosine we use it for many things on exams. You can use it to abort a super ventricular tachycardia when a vigus manover has not worked. I mean, not vigus. A vigal manover has not worked. You can also use it to treat because it actually in stress tests, in chemical stress tests, because you know, they are pretty under the purview of what we call the coronary steel principle. I've described that in a previous podcast, so they can be useful that purpose. So we can use adenosine for many different things. So you give a person adenosine and then you notice that their skin turns red.

Again, it's that cutinous, it's that cutinous of flushing reaction. And then you can even see a person that is taking like a herbal supplement to raise their HDL. That's myocene. Myocene has the ability to cause a cutinous of flushing. Or they can give you a question about a person that was recently pleased on some medication because you know, they presented originally with chest pain that's worsened with activity gets better with rest. This person has angina, right? They're probably taking a nitrate. Again, nitrates, they can dilate blood vessels because they can dilate blood vessels, especially veins. They can absolutely cause a cutinous of flushing. And remember, we can also see this problem with again, just many visual dilating agents, especially the calcium channel blockers, more specifically the dihydroperidine calcium channel blockers. These drugs, they have the ability to dilate vessels, they dilate more specifically the pre-capillary arterials because they can dilate those pre-capillary arterials. That visual dilation can cause a person to have a cutinous of flushing, right? Cutinous flushing. Or they can even give you some question about a person that is being treated for like a candidate like invasive candidate infection, right? They say that you know, the person has renal failure, so they elected to not give them footericin B. And then they give the person some drunk. And after giving that person that drunk, the person's that they have in cutinous flushing.

Well, you want to think about drugs like cuspophonjian, microphonjian, and anidunophonjian, right? Remember, these drugs are pretty good for the treatment of invasive candidate infections. In fact, in some settings, they are picked over and footericin B because we know that I'm footericin B has just profound nephrotoxicity, right? So in those circumstances, we try to go with these a, a kino-candins. Remember, the a kino-candins, essentially, the cell wall inhibitors in fungi world, right? They are the cell wall inhibitors in fungi world. The inhibitor, the enzyme called a 13 beta D-glucan synthase. The inhibitor, the enzyme, I'll say that again, 1,3 beta D-glucan synthase. Classic question and concerns step 3. Step 3 is one of those exams where every now and then you see the offhand data from a colochic question here like, well, when was it I see this? When I was maybe dusted up my first lead copy as a, as a first or second year medical student, right? Again, you kind of need to know the stuff for, especially for step 3. Every now and then they throw the stuff on, on step 2, right? So these a kino-candins, they can absolutely cause a, they can absolutely cause a cutinia of a visodilation, right? They can absolutely cause a cutinia of visodilation. But what if they give you a question about a person? Again, I want to keep this podcast kind of short, right?

But let's say they give you a question about a person, you know, they tell you that it's, you know, 25 years old, and he was recently placed on an anti-depressant because he had a tripping resistant depression. And then they tell you that he starts, he's been having orthostatic hypotension, he has been having cutinia's flushing, you know, he has been having a, like this fluttering feeling in his chest. And let me not say cutinia's flushing, my apologies there, but he's been having this fluttering feeling in his chest, he has been having orthostatic hypotension, he has just been feeling marshes, feeling very dizzy, right? And they tell you that sometimes he has like a fever and things like that. When you see stuff like this, I want you to think about TCA toxicity, try to slightly contain the present toxicity. The endgame is they absolutely love their TCA's, they really, really love their TCA's. And remember TCA's, you know, they're not a first-line agent for depression, they're more like a third-line agent cause they cause a lot of problems, right? Again, first things first, they have these anti-hamside effects. So please, I may spoke, they don't cause cutinia's flushing, right? So they're a hage, the stands for anti-hage one, right? So they have anti-histamine effects. So these drugs, they can cause sedation. But the A in the ham stands for anti-alpha one. So they can dilute blood vessels, they are literally alpha one blockers.

So they can cause orthostatic hypotension, especially when you combine them with another drug that is a prominent visual diluter, like a calcium channel blocker, especially a dihydroperidine, calcium channel blocker, or hydrozene, or like a nitrate, or you know, stuff like that, right? So they can cause orthostatic hypotension, right? And then the anti-mostchorinic effects, right, that M stands for anti-mostchorinic, they can cause like these hot as a hair and things like that, right? They can cause anti-chorinurgic side effects. So give them to a person that's elderly, those people could potentially, unfortunately, have delirium and fins and fins of that nature, right? But remember that potassium channel blockers, and I mean TCA is the tricyclic and tidy presence. They have a lot of other problems that they can cause, right? They literally can block sodium channels. They're sodium channel blockers, right? That's one of the reasons why they can cause EKG problems. In fact, the classic telltale sign on an Indian exam for potassium and TCA toxicity is a widening of the QRS. They can also prolong the QT interval, you know, but it can also widen your QRS complex, right?

And remember, that's one of the reasons why we give sodium bicarbonate, because since these drugs are sodium channel blockers, if you give sodium bicarb, you're essentially extracellularly delivering sodium that can outcompete that can essentially overwhelm the sodium channel blockade that happens with the TC Es, and that will be helpful in visa circumstances. Something you want to keep at the back of your mind, for example, actually, right? And again, because it can block sodium channels, it can prolong your QT interval. Whenever you have a QT interval prolongation, that can predispose you to truss out the point, right? In fact, the thing is, many of these drugs that you seek cost truss out the point, many times the common thread across those drugs is that in some way shape of form, have the ability to block either sodium channels or potassium channels, right? So again, if the Indian is asking about the mechanism behind like, truss out the point in a person taking a certain medication, just think about potentially sodium channel blockade as an answer, or potassium channel blockade as an answer, right? So what are the drugs that have the ability to prolong the QT interval and cause truss out the point? Well, don't forget, again, you'll try slightly counter-depressants that can cause this problem, right?

Or you think about these anti-psychotics, your anti-psychotics, again, some of them work on other channels besides, work on other things, besides just blocking dopamine receptors, right? They can absolutely prolong the QT interval, especially like Ziprasidone, right? Ziprasidone, I believe, is the drug known as Geodone, of all the anti-psychotics, actually, including Hallopereodone, is the one that has the strongest assertion of prolonging the QT interval, right? Or you think about like your undanced tron, right? Zofran, that many are forced to know, you know? Again, these drugs can prolong the QT interval, right? So if they tell you about the person having intersat the point and the answer for the mechanism, again, you may see sodium channel blockade as an answer, you may see potassium channel blockade as an answer, and other answer you may see is just from, you know, prolongation of the QT interval, right? Again, these are all like mechanism-based things that many people kind of struggle with, unfortunately, on exams, right? And also many of these antibiotics, right? Like your macrolids, your furrow quinolones, those things can all prolong the presence of QT interval, right? All these are, these are anti-fongals, right? Like, for example, for example, right? Those things can all prolong the QT interval, right? So again, these are all things you want to make sure you can keep at the back of your mind on exams, right?

Every now and then again, I'll just make these from a psychological side effect podcast because again, sadly, it's kind of like one of these high-yield weird things that every now and then just pops up on tests and people are like, oh, I don't know what to do concerning this. So I really hope you found this podcast to be helpful. I'm going to go ahead and pause here. Again, I do a four-one-one-one-one-one-limited basis for all the USMEL exams, step one-to-step three, pre-clean cool med school exams, 30-aclic-ship-shoff exams. I also offer review courses. That's what most people take advantage of. The 20-hour review course, the MBME testing and strategy scores, have a 20-hour review course literally starting this evening. And then I also have a bio-statistics bootcamp. That one's going to be taking place on the 21st of July. It's going to be a four-hour but very high-yield course. Again, I'm going to try to break down bio-statistics for you. So you're not just like the marising formulas, but you actually understand what in the world is going on with the subject matter. And then I have these podcasts, an Apple podcasts, or Google podcasts, and Spotify. I have a You Tube channel, many of you know, this Divine Intervention, USMELY podcasts and videos. That's why I post the videos that I make. And then I also have a new website called Divine Intervention Life Lessons.com. It's a Bible-based website. Many of you listen to this podcast from our Christian. So I made these podcasts.

They have about 10 to maybe 20 minutes longer than most. That I address like a classic topic that affects a lot of humans. I make like two podcasts every week. Usually, you know, I'm going to put them out two more tours the weekends. And we have almost a hundred episodes now. I actually have the podcast as well. An Apple podcast is called that Divine Intervention Life Lessons Podcast. So again, if you listen to you, probably be blessed. You're probably keen something from it. So I think I'm going to go ahead and pause here again. And I also help with Eras applications, you know, rec letters, personal statements, editing Eras applications, mock interviews, editing, supplemental applications, and things of that sort. So thank you for listening to me. Have a wonderful rest of your day. God bless you. See you next time. Thank you.

Methamphetamine intoxication usually presents with very prominent hallucinations, which is a core feature.

The tricuspid valve (right-sided heart).

TC As are anti-$\alpha_1$ agents, blocking alpha-adrenergic receptors and causing peripheral vasodilation.

1,3-$\beta$-D-glucan synthase.

Widening of the QRS complex (due to sodium channel blockade).

Vancomycin, Adenosine, Nitrates/Calcium Channel Blockers (e.g., Dihydropyridines), and Macrolides/NSAI Ds.

Inhibition of 1,3-$\beta$-D-glucan synthase (a cell wall component in fungi).

To ensure adequate systemic drug levels and bypass potential gastrointestinal absorption issues associated with severe infection.

Flushing, pruritus (itching), and hypotension/vasodilation.

Increased catecholamines (norepinephrine/epinephrine) at adrenergic synapses.

Anti-histamine effect (H1 blockade); $\alpha_1$ blocking effect (causes vasodilation leading to orthostatic hypotension).

Certain antiarrhythmics or macrolides; e.g., Azithromycin or Amiodarone.

Inhibition of 1,3-$\beta$-D-glucan synthase (a cell wall component in fungi).

To ensure adequate systemic drug levels and bypass potential gastrointestinal absorption issues associated with severe infection.

Flushing, pruritus (itching), and hypotension/vasodilation.

Increased catecholamines (norepinephrine/epinephrine) at adrenergic synapses.

Anti-histamine effect (H1 blockade); $\alpha_1$ blocking effect (causes vasodilation leading to orthostatic hypotension).

Certain antiarrhythmics or macrolides; e.g., Azithromycin or Amiodarone.